Bulletin of Pioneering Researches of Medical and Clinical Science
2024 Volume 3 Issue 2
Creative Commons License

Phytochemical and Ethnopharmacological Review of Aegle marmelos Linn. (Bael)

Mahendra Kumar Sahu*✉ , Sandip Prasad Tiwari
  1. MATS School of Pharmacy, MATS University, Raipur, CG 493441, India.
  2. Department of Pharmaceutical Sciences, Kalinga University, New Raipur, CG 492001, India.
Abstract

Aegle marmelos Linn. (Bael) is a fruit-bearing tree native to the Indian subcontinent. It holds a significant place in traditional medicine systems and cultural practices of the region. The aim of the study on A. marmelos phytochemical and pharmacological investigation of the bioactive compounds present in the plant and to elucidate their potential pharmacological activities. The goal of this research is to better understand ancient medicine and its possible uses in contemporary healthcare. A multidisciplinary approach combining botanical, phytochemical, and pharmacological approaches is required to understand A. marmelos. The results of a pharmacological and phytochemical study on A. marmelos would provide valuable insights into its potential health benefits and the bioactive compounds responsible for those effects. In summary, A. marmelos is a plant with significant potential for promoting health and well-being, based on both traditional wisdom and emerging scientific knowledge. Its wide range of bioactive compounds makes it an intriguing subject for further research and exploration into its therapeutic applications‎.

Keywords: Aegle marmelos, Phytoconstituents, Medicinal Property, Pharmacology

Introduction

Aegle marmelos Linn. (Bael) is an important medicinal tree in India, commonly known as Bael fruits, Bel, Indian Bael, Bengal Quince, Belan in English and Shivadruma in Sanskrit, Bel or Bael in Hindi [1]. Fruits are green, hard, and smooth woody shells, that belong to the family Rutaceae. Geographically occurring as wild throughout Berma and cultivated at the Sub-Himalayan tract all over India, particularly Central as well as Southern India [2, 3]. This particular variety of trees, which is around 12 meters tall, sheds its leaves every autumn. The Hindu faith holds significant mythological value for the Leaf of the AM tree, often referred to as Tripatra, which is crucial for the Lord Shiva puja. The plant has tough, 8-9 meters in height, aromatic leaves, and round-shaped fruit 5-10 cm in diameter and mucilaginous in taste. Fruits are collected in April–May [4, 5]. Each parts of this tree are used and can be utilized in various fields [6]. A. marmelos is a high source of different phytochemicals i.e. carotenoids, terpenoids, alkaloids, flavonoids, amino acids, tannins, organic acids fatty acids, etc [7]. The formulation of AM is very well-known in history and is used in dysentery and diarrhea. The root is one of the essential parts used in herbal formulations such as Dashmularisht. Leaves contain alkaloids which play a role in reducing blood sugar levels [8]. Seeds are a rich source of oil and possess antibacterial, antiprotozoal along antifungal properties. It works in dose dose-dependent manner it may cause abortion as a result, it should not be used by pregnant women [9].

The taxonomical classification of Aegle marmelos is presented in Figure 1.

 

 

Figure 1. Taxonomical classification of Aegle marmelos

 

 

The aim of the study on A. marmelos phytochemical and pharmacological investigation of the bioactive compounds present in the plant and to elucidate their potential pharmacological activities.

 

Results and Discussion

Phytochemical’s

A. marmelos, commonly referred to as bael or Bengal quince, Ayurveda, and Traditional Chinese Medicine both use medicinal plants as part of their long-standing regimens [10]. A. marmelos is well renowned for having a variety of therapeutic benefits and these are attributed to the presence of numerous phytochemicals in its different parts, including leaves, fruits, and roots. Phytochemicals are naturally occurring bioactive compounds found in plants that often contribute to their potential health benefits [11-13]. The A. marmelos leaves, roots, and fruits have a variety of chemical constituents Hydro-alcohol is mostly used as a solvent for the extraction of active ingredients from this plant (Figure 2).

 

 

Figure 2. Phytoconstituents and uses of Bael Extract

 

 

Literature surveys suggested that A. marmelos contains a variety of phytochemicals [14]. Alkaloids are used medicinally to treat heart conditions, reduce inflammation, and provide anesthesia. Leukaemia, renal cell carcinoma, and prostate cancer were treated with coumarin, terpenoids, and flavonoids. Phenolic as well as amino acids play’s role as antioxidants and improve digestive system function (Table 1) [15].

 

 

Table 1. Eagle marmelos chemical composition, separation technique, and medicinal uses

S. No.

Metabolites

Phytochemicals

IUPAC Name

Molecular structure

Extraction/ Separation Technique

Pharmacology

Reference
  1.  

Alkaloid’s

Marmeline

(Z)-N-(2-hydroxy-2-(4-((3-methylbut-2-en-1-yl)oxy)phenyl)ethyl)-3-phenylacrylamide

Chromatography Techniques

Cardioprotective, Anaesthetic, anti-inflammatory, Anticancer

[16, 17]

Halfordino

4-(2-(pyridine-3-yl)oxazole-5-yl)phenol

[18-20]

Ethyl cinnamate

N-ethylcinnamamide

[21-24]

Aegelinosides a

N-((S)-2-(4-methoxyphenyl)-2-(((2R,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl)oxy)ethyl)cinnamamide

[25]

Aegelinosides b

(Z)-N-[(2S)-2-(4-methoxyphenyl)-2-[(2R,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxyethyl]-3-phenylprop-2-enamide

[26, 27]

Ethyl cinnamate

ethyl (E)-3-phenyl prop-2-enoate

[13, 28, 29]

Ethyl-cinnamon

N-ethylcinnamamide

[30, 31]

Ethanediamine

N-(2-ethoxy-2-(4-methoxyphenyl)ethyl)cinnamamide

[30]

Ethyl Cinnamide

N-(2-hydroxy-2-(4-((3-methylbut-2-en-1-yl)oxy)phenyl)ethyl)cinnamamide

[31, 32]

Aegelin

N-(2-hydroxy-2-(4-methoxyphenyl)ethyl)cinnamamide

[33-35]

Dictamine

4-methoxyfuro[2,3-b]quinoline

[36]

Aegelin

N-(2-hydroxy-2-(4-methoxyphenyl)ethyl)cinnamamide

[37, 38]

Fragrine

4,8-dimethoxyfuro[2,3-b]quinoline

[25, 39]

Eicosapentaenoic acid

(5E,8E,11E,14E,17E)-icosa-5,8,11,14,17-pentaenoic acid

[40, 41]

Omethylhalfordinine

5-(4-((3-methylbut-2-en-1-yl)oxy)phenyl)-2-(pyridin-3-yl)oxazole

[42, 43]

N-4-methoxystyryl cinnamide

methyl (E)-3-(4-methoxyphenyl)acrylate

[26, 44, 45]

Oisopentenyl halfordinol

isopentyl isobutyrate

[46, 47]

N-2-ethoxy-2-(4-methoxy phenyl) ethyl cinnamide

N-(2-ethoxy-2-(4-methoxyphenyl)ethyl)cinnamamide

[45, 48]

Marmelosin

9-((3-methylbut-2-en-1-yl)oxy)-7H-furo[3,2-g]chromen-7-one

[33, 49-52]

Marmin

(R, E)-7-((6,7-dihydroxy-3,7-dimethyloct-2-en-1-yl)oxy)-2H-chromen-2-one

[53-55]

3marmesin

(S)-2-(2-hydroxypropan-2-yl)-2,3-dihydro-7H-furo[3,2-g]chromen-7-one

[56-58]

Rutacine

2-(3,4-dihydroxyphenyl)-5,7-dihydroxy-3-(((2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-((((2R,3R,4R,5R,6S)-3,4,5-trihydroxy-6-methyltetrahydro-2H-pyran-2-yl)oxy)methyl)tetrahydro-2H-pyran-2-yl)oxy)-4H-chromen-4-one

[59, 60]

  1.  

Coumarin’s

Marmelosin

9-((3-methylbut-2-en-1-yl)oxy)-7H-furo[3,2-g]chromen-7-one

Chromatographic separation

Prostate cancer, renal cell carcinoma, and leukemia

[49, 61, 62]

Methyl ether

methoxymethane

 [63-65]

Scoparome

6,7-dimethoxy-2H-chromen-2-one

[66]

Imperatorin

9-((3-methylbut-2-en-1-yl)oxy)-7H-furo[3,2-g]chromen-7-one

[67, 68]

Umbelliferone

7-hydroxy-2H-chromen-2-one

[69-71]

Marmelide

9-((3-methylbut-2-en-1-yl)oxy)-7H-furo[3,2-g]chromen-7-one

[72, 73]

Mermenol

(E)-7-((2,6-dihydroxy-7-methoxy-7-methyloct-3-en-1-yl)oxy)-2H-chromen-2-one

[74]

Scopoletin

(E)-7-((2,6-dihydroxy-7-methoxy-7-methyloct-3-en-1-yl)oxy)-2H-chromen-2-one

[75]

Psoralen

7H-furo[3,2-g]chromen-7-one

[76]

Alloimperaterin

9-hydroxy-4-(3-methylbut-2-en-1-yl)-7H-furo[3,2-g]chromen-7-one

[77]

Zanthotaxol

9-hydroxy-7H-furo[3,2-g]chromen-7-one

[78]

Epoxyauraptan

(E)-7-((3,7-dimethylocta-2,6-dien-1-yl)oxy)-2H-chromen-2-one

[79]
  1.  

Terpenoid

Alpha phellandrene

5-isopropyl-2-methylcyclohexa-1,3-diene

Hydrodistillation, steam distillation, and solvent extraction

Immune modulator, antifungal, antiviral, antiparasitic, antispasmodic, antihyperglycemic

[80]

3-Carvomenthenol

6-isopropyl-3-methylcyclohex-2-en-1-ol

[31, 81-83]

Pentamethylene glycol

pentane-1,5-diol

Dipentene

1-methyl-4-(prop-1-en-2-yl)cyclohex-1-ene

Ocimene

7-methyl-3-methyleneocta-1,6-diene

Australene

2,6,6-trimethylbicyclo[3.1.1]hept-2-ene

[32]

Delta-3-Carene

3,7,7-trimethylbicyclo[4.1.0]hept-3-ene

[30]

Β-ocimene

(E)-3,7-dimethylocta-1,3,6-triene

[84]

Boisvelon

1-(2,3,8,8-tetramethyl-1,2,3,4,5,6,7,8-octahydronaphthalen-2-yl)ethan-1-one

[39]

Licareol

3,7-dimethylocta-1,6-dien-3-ol

[85]

Isoterpinene

1-methyl-4-(propan-2-ylidene)cyclohex-1-ene

 

Moslene

1-isopropyl-4-methylcyclohexa-1,4-diene

 

Butanoic acid

5-isopropyl-2-methylbicyclo[3.1.0]hexan-1-ol

[32]

Thujen-3en-10-ol

(5-isopropylbicyclo[3.1.0]hex-2-en-2-yl)methanol

Delta - elemene

(3R,4R)-1-isopropyl-4-methyl-3-(prop-1-en-2-yl)-4-vinylcyclohex-1-ene

 

Terpinen-4-ol

1-isopropyl-4-methylcyclohex-3-en-1-ol

 

Alpha-cubebene

4-isopropyl-3,7-dimethyl-3a,3b,4,5,6,7-hexahydro-1H-cyclopenta[1,3]cyclopropa[1,2]benzene

Theta element

(1S,2S)-1-methyl-2-(prop-1-en-2-yl)-4-(propan-2-ylidene)-1-vinylcyclohexane

Alpha humulene

(1E,4E,8E)-2,6,6,9-tetramethylcycloundeca-1,4,8-triene

Theta morpholine

1-isopropyl-7-methyl-4-methylene-1,2,3,4,4a,5,6,8a-octahydronaphthalene

Theta curcumene

1-methyl-4-(6-methylhept-5-en-2-yl)cyclohexa-1,3-diene

Farnesyl pyrophosphate

(3R,4aS,5R)-4a,5-dimethyl-3-(prop-1-en-2-yl)-1,2,3,4,4a,5,6,7-octahydronaphthalene

Eudesmane

4a-methyl-1-methylene-7-(prop-1-en-2-yl)decahydronaphthalene

 

Sisquiterpenoid

1-methyl-4-(6-methylhepta-1,5-dien-2-yl)cyclohex-1-ene

 

Levomenol

(S)-4-methyl-1-((S)-6-methylhept-5-en-2-yl)cyclohex-3-en-1-ol

Theta cardinene

1-isopropyl-7-methyl-4-methylene-1,2,3,4,4a,5,6,8a-octahydronaphthalene

Alpha terphenyl isobutyrate

2-(4-methylcyclohex-3-en-1-yl)propane-2-yl isobutyrate

Cis, Trans Farnesol

(2E,6E)-3,7,11-trimethyldodeca-2,6,10-trien-1-ol

2-cis, 6-trans- Farnesol

(2Z,6E)-3,7,11-trimethyldodeca-2,6,10-trien-1-ol

3z-hexenol

(Z)-hex-1-en-1-ol

Ethyl hexoic acid

ethyl hexanoate

[31]

Methyl Perillate

methyl (2E,4E)-5-(benzo[d][1,3]dioxol-5-yl)penta-2,4-dienoate

[30]

Alpha-Cardinol

(1R,4S,4aR,8aR)-4-isopropyl-1,6-dimethyl-1,2,3,4,4a,7,8,8a-octahydronaphthalen-1-ol

Eucalyptol

1,3,3-trimethyl-2-oxabicyclo[2.2.2]octane

 

Limonene oxide

(1S,4R)-1-methyl-4-(prop-1-en-2-yl)-7-oxabicyclo[4.1.0]heptane

Α-cedrene

(3R,3aS,7S,8aS)-3,6,8,8-tetramethyl-2,3,4,7,8,8a-hexahydro-1H-3a,7-methanoazulene

Α-copaene

(1S,6S,7S,8S)-8-isopropyl-1,3-dimethyltricyclo[4.4.0.02,7]dec-3-ene

Cis-

Linalool oxide

6-methyl-2-(oxiran-2-yl)hept-5-en-2-ol

Elemol

2-((1R,3S,4S)-4-methyl-3-(prop-1-en-2-yl)-4-vinylcyclohexyl)propan-2-ol

 

Alpha zingiberene

2-methyl-5-(6-methylhept-5-en-2-yl)cyclohexa-1,3-diene

 

Epicubenol

(3S,3bS,4S,7S,7aS)-4-isopropyl-3,7-dimethyl-2,3,3a,3b,4,7-hexahydro-1H-cyclopenta[1,3]cyclopropa[1,2]benzen-3-ol

[31]

Dipentene

1-methyl-4-(prop-1-en-2-yl)cyclohex-1-ene

 

Cannabinoid

(1R,9S,E)-4,11,11-trimethyl-8-methylenebicyclo[7.2.0]undec-4-ene

 

Alpha ocimene

(Z)-3,7-dimethylocta-1,3,7-triene

 

Epicubenol

(1S,4R,4aR,8aR)-1-isopropyl-4,7-dimethyl-1,3,4,5,6,8a-hexahydronaphthalen-4a(2H)-ol

 

Alpha humulene

(1E,4E,8E)-2,6,6,9-tetramethylcycloundeca-1,4,8-triene

 

Beta myrcene

7-methyl-3-methyleneocta-1,6-diene

 

Alpha copaene

(1S,6S,7S,8S)-8-isopropyl-1,3-dimethyltricyclo[4.4.0.02,7]dec-3-ene

 
  1.  

Phenolic acid’s

Chlorogenic acid

(1S,3R,4R,5R)-3-(((E)-3-(3,4-dihydroxyphenyl)acryloyl)oxy)-1,4,5-trihydroxycyclohexane-1-carboxylic acid

Column Chromatography

 

Antioxidant’s

 

Rutaretin

(S)-9-hydroxy-2-(2-hydroxypropan-2-yl)-2,3-dihydro-7H-furo[3,2-g]chromen-7-one

 

Gallic acid

3,4,5-trihydroxybenzoic acid

 

Vanillic acid

4-hydroxy-3-methoxybenzoic acid

 

Caffeic acid

(E)-3-(3,4-dihydroxyphenyl)acrylic acid

 

Gentisic acid

2,5-dihydroxybenzoic acid

 

Syringic acid

4-hydroxy-3,5-dimethoxybenzoic acid

 

Procatechuic acid

3,4-dihydroxybenzoic acid

 

Ferulic acid

(E)-3-(4-hydroxy-3-methoxyphenyl)acrylic acid

 

P- coumaric

Acid

(E)-3-(4-hydroxyphenyl)acrylic acid

 
  1.  

Flavonoid’s

Quercetin

2-(3,4-dihydroxyphenyl)-3,5,7-trihydroxy-4H-chromen-4-one

Chromatographic techniques

anticancer, antioxidant, anti-inflammatory, and antiviral properties

[10]

 

 

Rutin

2-(3,4-dihydroxyphenyl)-5,7-dihydroxy-3-(((2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-((((2R,3R,4R,5R,6S)-3,4,5-trihydroxy-6-methyltetrahydro-2H-pyran-2-yl)oxy)methyl)tetrahydro-2H-pyran-2-yl)oxy)-4H-chromen-4-one

[18]

 

 

Catechin

(2R,3S)-2-(3,4-dihydroxyphenyl)chromane-3,5,7-triol

 

 

 

Flavan-3-ol

2-phenylchroman-3-ol

 
  1.  

Carotenoid’s

Skimminianine

2-phenylchroman-3-ol

Chromatography

Antioxidants, immunomodulator

 

4, 7, 8-trimethoxyfuro-quinoline

4,7,8-trimethoxyfuro[2,3-b]quinoline

 
  1.  

Tannin’s

Alanine

(2S)-2-aminopropanoic acid

Extraction technique

Antidote, antiseptic and astringent

 

Phenyl alanine

(2S)-2-amino-3-phenylpropanoic acid

 

Tyrosine

L-tyrosine

 

Leucine

(2S)-2-amino-4-methylpentanoic acid

 

Methionine

(2S)-2-amino-4-methylsulfanylbutanoic acid

[14]

Isoleucine

(2S,3S)-2-amino-3-methylpentanoic acid

Aspartic acid

(2S)-2 -aminobutanedioic acid

Arginine

(S) - 2-Amino - 5-guanidinopentanoic acid
  1.  

Amino acid’s

Phenyl alanine

(2S) – 2 –amino - 3-phenylpropanoic acid

Ion exchange, metal affinity, and gel filtration chromatography

Body proteins, neurotransmitter’s, and Hormones synthesis

 

Tyrosine

(2S)-2-amino-3-(4-hydroxyphenyl)propanoic acid

 

Leucine

(S)-2-amino-5-((diaminomethylene)amino)pentanoic acid

Methionine

(2S)-2-amino-4-methylsulfanylbutanoic acid

 

Isoleucine

(2S,3S)-2-amino-3-methylpentanoic acid

[25]

Aspartic acid

(2S)-2-aminobutanedioic acid

 

Arginine

(S)-2-amino-5-((diaminomethylene)amino)pentanoic acid

Alanine

(2S)-2-aminopropanoic acid

 
  1.  

Organic acid’s

Oxalic acid

Oxalic acid

anion exchange, ion exclusion, and reversed-phase high-performance liquid chromatography

Antimicrobials, preservatives, and sanitizers

 

Malic acid

2-hydroxysuccinic acid

 

Tartaric acid

(2R,3R)-2,3-dihydroxysuccinic acid

 
  1.  

Fatty acid’s

Linoleic

(9Z,12Z)-octadeca-9,12-dienoic acid

Low-temperature crystallization, distillation, and precipitation techniques

Gene regulation, membrane component formation, and source of energy

 

Palmitic

Hexadecanoic acid

 

Stearic

Octadecanoic acid

[62]

Linolenic acid

(9Z,12Z,15Z)-octadeca-9,12,15-trienoic acid

 

Oleic acid

(Z)-octadec-9-enoic acid

Ricinoleic acid

(R, Z)-12-hydroxyoctadec-9-enoic acid

 

Stearic acid

Octadecanoic acid

 

Linolenic acid

(9Z,12Z,15Z)-octadeca-9,12,15-trienoic acid

 

Tetradecanoic acid

tetradecanoic acid

 

Pentadecanoic acid

pentadecanoic acid

 

Palmitoleic acid

(Z)-hexadec-9-enoic acid

 

 

 

Medicinal and pharmacological properties

Anticancer activity

Studies suggested that certain compounds found in bael, including alkaloids and essential oils, may exhibit cytotoxic effects on cancer cells [19]. A. marmelos extract shows significant inhibition on MCF 7 and MDAMB 231 breast cancer cell lines [6]. These compounds could interfere with the growth and division of cancer cells, leading to their destruction (Figure 3) [19].

 

Figure 3. Anticancer effect of AM

Antidiabetic activity

Diabetes mellitus is a common metabolic disorder [72, 86]. A. marmelos hydro-alcoholic extract helps to reduce the blood sugar level as well as significantly increase the blood insulin and liver glycogen in diabetic rats [10, 42].

 

Anti-ulcer activity

Currently, due to lifestyle gastric disorders are common, Researchers reported that the methanolic extract of bael is highly effective for reducing gastrointestinal ulcers [35, 47].

Antimicrobial activity

The antibacterial activity of the different A. marmelos extracts were tested quinine compound was identified as possessing good antibacterial activity [66]. Researchers found that extract is highly effective as compared to other allopathic preparations against gram-positive and negative bacteria (Figure 4) [18, 55].

 

Figure 4. Antibacterial effect of AM

Antioxidant activity

Oxidative stress is induced due to physical, chemical, environmental as well as biological factors which cause the generation of free radicals [51]. A. marmelos phytoconstituents play a crucial role in free radical scavenging, these alteration returns the free radical to normal levels which reveals the antioxidant activity of bael extract [67, 83].

Anti-hyperlipidemic activity

Literature surveys reveal that bael extract induces the utilization of elevated fatty acids and their types [74]. As a result, lower levels of fatty acids were formed which is an important channel for consumption of higher glucose molecules [58].

Radioprotective action

In recent times radiotherapy has been one of the important causes of cancer because of its free radical formation-inducing property. A. marmelos extract was reported for the free radical scavenging of radiation-induced free radicals [73]. The radioprotective activity was studied in Swiss albino rats that were given a lot of intraperitoneal single doses of the extract [74].

Antiviral activity

The ability of different varieties of fungi to grow is tested by the separated volatile oil from A. marmelos [72]. The essential oil fully stopped all fungi from generating spores at a dosage of 0.05%. Around 75% and 90% of the fungus are significantly suppressed at 0.03%- 0.04%, respectively (Figure 5) [66].

 

Figure 5. Antiviral of A. marmelos

Conclusion

The present study suggested that the therapeutic potential of AM and the phytoconstituents may be utilized to develop unique formulations for the management, mitigation as well as prevention of cancer, diabetes mellitus, and other microbial diseases [47]. Numerous ethnobotanical uses of AM have been documented in the past. Unfortunately, the majority of substances still need to be carefully examined to look into new lead molecules or pharmacophores. A few bioactive compounds' processes have also so far been identified. To determine the pathophysiology as well as the pharmacology of various phytochemicals with the efficacy of AM pharmacological properties, extensive research is required [1].

Acknowledgments: The principal of the MATS School of Pharmacy in Raipur, Dr. Amit Nayak, is acknowledged by one of the authors for his consistent support and inspiration.

Conflict of interest: None.

Financial support: None.

Ethics statement: None.

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How to cite this article
Vancouver
Sahu MK, Tiwari SP. Phytochemical and Ethnopharmacological Review of Aegle marmelos Linn. (Bael) . Bull Pioneer Res Med Clin Sci. 2024;3(2):29-47.
APA
Sahu, M. K., & Tiwari, S. P. (2024). Phytochemical and Ethnopharmacological Review of Aegle marmelos Linn. (Bael) . Bulletin of Pioneering Researches of Medical and Clinical Science, 3(2), 29-47.
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